During recent years transgenic animal models have become important research tools for studying the genetic causes of human disease. Micro- imaging in vivo provides a powerful tool to monitor animals longitudinally to assess the response to various forms of intervention and to quantify genotypic variations of development during growth. Micro- imaging further plays an increasingly important role for the study of tissue structure and function. Unlike histomorphometry, 3D microimaging is non-destructive and provides detailed information on the three-dimensional architecture of mineralized tissue, as well as the location and density of calcification. In this application, a broad range of investigators seeks funding for the acquisition of a novel microcomputed tomography (mu-CT) system for 3D microscopic imaging. The requested instrument is unique in that it is capable of imaging 1-inch specimens at an isotropic resolution of 25mu m as well as small rodents in vivo at 50/mu m resolution. The instrument is designed around a rotating gantry involving cone-beam scanning and reconstruction. The mu-CT scanner complements magnetic resonance micro-imaging widely used at the investigators' institution and provides new capabilities not currently available. Targeted applications of the proposed equipment include quantification of the micro-architecture and local mineral density of calcified tissues, in particular trabecular and cortical bone from human cadavers and bone biopsies, calcified heart valves and atherosclerotic plaques. The in vivo applications are aimed at the study of gene expression in genetically altered mice. Specific projects enhanced by the requested equipment involve the serial evaluation of metastatic cancer, the assessment of arterial wall calcification in marine models of atherosclerosis and the assessment of the response to therapy. Other funded projects benefitting from the requested instrument include the study of osteogenesis in mice lacking the AKL. bone morphogenetic protein receptor, the evaluation of the mechanism of regulation of apoptosis in endochondral bone formation, the quantification of craniofacial structure in mouse models of sleep apnea, and the study of tissue engineering of the intervertebral disc.